Ca2+ Sensitization of Myocardial Force and Actomyosin ATPase by (D-Ala2, Met5) Enkephalinamide

Abstract

The presence of proenkephalin mRNA and proenkephalin peptides in cardiac muscle cells suggests the local production of enkephalins in the myocardium. Yet, the effects of these peptides on the function of the contractile proteins are unknown. The effects of (D-Ala2, Met5) enkephalinamide (DALA) on the activity of the actin stimulated Ca, Mg-myosin ATPase in myofibrils and on the contractility and the activity of the related actomyosin ATPase of chemically skinned muscle fibres from pig myocardium were studied. In this article, it is shown that the myofibrillar actomyosin ATPase as well as the contractility and the actomyosin ATPase in skinned fibres are sensitized to Ca2+ ions by DALA. 10(-11) -10(-6) mol/l DALA decrease the effective concentration of Ca2+ stimulating the myofibrillar ATPase activity by 50% (EC50) from 4.0.10(-5) to 1.5.10(-5) mol/l (p < 0.05). The magnesium dependent myosin ATPase activity at low Ca2+ concentration (10(-9) mol/l) is increased. The EC50 values of Ca2+ for both force development and the related actomyosin ATPase activity of skinned fibres are decreased by DALA (10(-11) -10(-5) mol/l) from 2.5.10(-6) to 2.0.10(-6) mol/l (contractions; p < 0.01) and from 2.0.10(-6) to 1.3.10(-6) mol/l (ATPase activity; p < 0.01). The tension cost (ATPase/tension) of the fibres is unchanged by DALA. In conclusion, the results demonstrate a Ca2+ sensitization of the contractile proteins by low concentrations of DALA, indicating a direct regulatory involvement of enkephalins in the regulation of myocardial contractility. These results correspond with the positive inotropic effects of enkephalins in isolated heart muscle cells.